Synthesis and anti-HIV-1 activity of novel 2,3-dihydro-7H-thiazolo[3,2-a]pyrimidin-7-ones.
Appropriately substituted 2,3-dihydro-7H-thiazolo[3,2-a]pyrimidin-7-ones 9-12 and 18 were considered as annulated analogues of HEPT (1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine), and some of these compounds were also found active against HIV-1, the most active one being 2,3-dihydro-5-[(3,5-dimethylphenyl)methyl]-3-ethoxy-6-ethyl-7H- thiazolo[3,2-a]pyrimidin-7-one (10b). S-Alkylation of 5-alkyl-6-(arylmethyl)-2-thiouracils 1-4 was performed with 2-bromoacetaldehyde acetals to furnish the S-[bis(alkoxy)ethyl] derivatives 5-8 and with allyl bromide to furnish S-allyl derivatives 17. The target compounds 9-12 were obtained by an N1 regioselective intramolecular cyclization reaction of silylated 5-8 using trimethylsilyl trifluoromethanesulfonate (TMS triflate) as the catalyst. Treatment of the S-allyl derivatives 17 with bromine in dry methylene chloride afforded the 3-(bromomethyl) derivatives 18.
Danel
K
K
Department of Chemistry, Odense University, Denmark.
Pedersen
E B
EB
Nielsen
C
C
D000478:Alkylation; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008698:Mesylates / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011744:Pyrimidinones / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013941:Thymine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D014498:Uracil / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
C110622:2,3-dihydro-7H-thiazolo(3,2,a)pyrimidin-7-one; D019380:Anti-HIV Agents; C092123:DABO 546; D008698:Mesylates; D011743:Pyrimidines; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D013844:Thiazoles; C061818:1-((2-hydroxyethoxy)methyl)-6-(phenylthio)thymine; D014498:Uracil; D054303:HIV Reverse Transcriptase; C012077:trifluoromethanesulfonic acid; D013941:Thymine; C083858:emivirine